title: Vascular remodeling and arterial calcification are directly mediated by S100A12 (EN-RAGE) in chronic kidney disease.
abstract: BACKGROUND
  The proinflammatory cytokine S100A12 (also known as EN-RAGE) is associated with cardiovascular morbidity and mortality in hemodialysis patients. In the current study, we tested the hypothesis that S100A12 expressed in vascular smooth muscle in nonatherosclerosis-prone C57BL/6J mice on normal rodent chow diet, but exposed to the metabolic changes of chronic kidney disease (CKD), would develop vascular disease resembling that observed in patients with CKD.
  
  
  METHODS
  CKD was induced in S100A12 transgenic mice and wild-type littermate mice not expressing human S100A12 by surgical ligation of the ureters. The aorta was analyzed after 7 weeks of elevated BUN (blood urea nitrogen), and cultured aortic smooth muscle cells were studied.
  
  
  RESULTS
  We found enhanced vascular medial calcification in S100A12tg mice subjected to CKD. Vascular calcification was mediated, at least in part, by activation of the receptor for S100A12, RAGE (receptor for advanced glycation endproducts), and by enhanced oxidative stress, since inhibition of NADPH-oxidase Nox1 and limited access of S100A12 to RAGE attenuated the calcification and gene expression of osteoblastic genes in cultured vascular smooth muscle cells.
  
  
  CONCLUSIONS
  S100A12 augments CKD-triggered osteogenesis in murine vasculature, reminiscent of features associated with enhanced vascular calcification in patients with chronic and end-stage kidney disease.
authors.affiliation: Sections of Cardiology, Department of Medicine, University of Chicago, IL 60637, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gawdzik
authors.forename: Liby
authors.initials: L
authors.lastname: Mathew
authors.forename: Gene
authors.initials: G
authors.lastname: Kim
authors.forename: Tipu S
authors.initials: TS
authors.lastname: Puri
authors.forename: Marion A
authors.initials: MA
authors.lastname: Hofmann Bowman
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D002114:Calcinosis / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism*; D000067616:S100A12 Protein; D014652:Vascular Diseases / Q000378:metabolism*
chemical_list: D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human